Colon Cancer Cells Use Mysterious RNA Strands to Avoid Cell Death

New study paves way for novel therapeutics. (Credit: Pixabay)

Researchers have discovered how unusually long strands of RNA help colon cancer cells to avoid death, allowing unregulated growth. 

Unlike other RNAs, the intriguing strands do not appear to encode proteins and are termed long non-coding RNAs or lincRNAs. 

In the new study published in Scientific Reports, researchers compared lincRNA levels inside tumour cells, to levels inside healthy colon cells.

They found over 200 lincRNAs at significantly different levels inside the tumour cells as compared to normal cells. One, in particular, called lincDUSP, was overexpressed in 91% of the tumour samples. A few tumours had more than fifteen times the normal amount of lincDUSP.

 

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The significant increase suggested this mysterious, and previously uncharacterised, RNA could be cancer-causing.

“To determine whether lincDUSP shows oncogenic activity in colon cancer, we decided to test the effects of depleting lincDUSP in patient-derived colon tumour cell lines,” the authors wrote. 

The researchers genetically modified colon cancer cells to deplete lincDUSP, and surprisingly, the cells began replicating at normal rates. They no longer had unrestricted growth associated with colon cancer tumour cells. Small molecules that inhibit lincDUSP, say the researchers, could have similar effects.

“Our work demonstrates that not only protein-coding genes but also non-coding genes contribute to colon cancer progression,” says Ahmad Khalil, PhD, senior author, assistant professor of genetics and genome sciences at Case Western Reserve University School of Medicine. 

“LincRNAs could be exploited as direct drug targets in this and other human diseases.”

 

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Khalil’s team discovered that depleting lincDUSP restored inherent cell death mechanisms. Colon cancer cells with low levels of lincDUSP became susceptible to cellular checkpoints that keep growth in check.

They immediately committed cell suicide — apoptosis — at the first sign of DNA damage. Depleting the single lincRNA also had widespread genetic effects.

The team discovered that reducing lincDUSP levels affected expression of over 800 other genes.

 

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These results, combined with the team’s experiments showing lincDUSP interacting with DNA, add to a growing body of evidence that lincRNAs are central to gene regulation. As such, they could represent an intriguing arena for drug developers.

“Not much is known about the role of long non-coding RNAs in colon cancer,” Khalil continued. “Using new technologies that target RNA molecules, instead of proteins, adds a new dimension to cancer therapies.”

 


Materials provided by Case Western Reserve University. Note: Content may be edited for style and length.